The long-term goal of this research program is to elucidate the mechanism of action of thyroid hormones at the cellular level through a study of the relationships between hormone-receptor interactions, hormone actions and hormone metabolism. The research proposed in this application is concerned primarily with a study of binding interactions between thyroid hormones and components of amphibian hepatic tissue, in order to determine the presence, location and properties of putative hormone receptors. Binding interactions will be studied following exposure of tadpoles to hormones in vivo (by injection techniques) and in vitro using an isolated liver cell preparation. Evidence that certain binding sites are hormone receptors will be obtained from their properties (e.g. specific, high affinity, low capacity sites) and by comparing the relative affinities of the sites of thyroxine analogues with the relative biological potencies of these analogues in this species. The presence of putative receptors will then be assessed in tadpoles at different stages of development and the findings correlated with the appearance and subsequent activity of hepatic carbamyl phosphate synthetase, an enzyme whose synthesis is induced by thyroid hormone. Similar binding studies will be performed in the adult frog and Necturus, forms which are generally thought to be unresponsive to thyroid hormone.